阻断白介素-17A对博来霉素诱导小鼠肺纤维化及miRNA-21表达的影响

Influence of Blocking Interleukin-17A on Bleomycin-Induced Pulmonary Fibrosis and Expression of miRNA-21 in Mice

目的探讨阻断白细胞介素-17A(interleukin-17,IL-17)对博来霉素诱导小鼠肺纤维化及miRNA-21表达的影响。方法 80只小鼠随机分为假手术组、模型组、同型抗体对照组(IgG2A组)、IL-17A抗体干预组各20只。模型组、IgG2A组、IL-17A抗体干预组小鼠气管内注射博来霉素(bleomycin,BLM)致急性肺损伤诱导肺纤维化形成,假手术组给予等量生理盐水。造模后第4、9、14、19、22天IL-17A抗体干预组尾静脉注射IL-17A中和抗体,IgG2A组注射同型对照抗体IgG2A;模型组和假手术组注射等量生理盐水。造模后培养第7、14、28天4组小鼠分批处死。比较各组小鼠在不同时间点肺组织病理学变化积分、肺系数、miRNA-21表达水平的变化。结果与模型组比较,IL-17A抗体干预组在各时间点肺组织病理学变化积分、肺系数、miRNA-21表达水平均有显著改变,差异具有统计学意义(P<0.05);IgG2A组在各时间点上述指标与模型组比较无显著差异(P>0.05)。结论阻断IL-17A可通过降低miRNA-21的表达延缓肺纤维化进程。

Objective To investigate the effect of blocking interleukin-17A(IL-17A)on bleomycin-induced pulmonary fibrosis and miRNA-21 expression in mice. Methods 80 mice were randomly divided into 4 groups:sham operation group,model group,homotype antibody control group(IgG2A group),and IL-17A antibody intervention group,with 20 mice in each group.Bleomycin(BLM)was injected into mice’s trachea to induce acute lung injury and pulmonary fibrosis in model group,IgG2A group and IL-17A antibody intervention group,and mice in sham operation group were given the same amount of saline.On the 4th,9th,14th,19th and 22th day after model establishment,IL-17A neutralizing antibody was injected into tail vein of IL-17A antibody ntervention group,and IgG2A into tail vein of IgG2A group;mice in model group and sham operation group were injected with the same amount of saline.On the 7th,14th and 28th day of culture after model establishment,mice of 4 groups were sacrificed in batches.The pathological change scores of lung tissue,lung coefficient,expression of miRNA-21 in different groups at different time points were compared. Results Compared with the model group,pathological change score of lung tissue,pulmonary coefficient,expression of miRNA-21 in the IL-17A antibody intervention group varied significantly at each time point,and the difference was statistically significant( P <0.05).Compared with the model group,there was no significant change in above indicators at each time point in IgG2A group( P >0.05). Conclusion Blocking IL-17A can inhibit the progression of pulmonary fibrosis by decreasing miRNA-21 expression.